Characterization of the transcription factor Gfi1 as novel regulator of bone homeostasis

转录因子 Gfi1 作为骨稳态调节剂的表征

• 批准号: 169478868
• 负责人: Professor Dr. Stefan Mundlos
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/169478868?language=en
• 关键词: Characterization; transcription; factor; Gfi1; novel

The transcription factor growth factor independent 1 (GFI1) is a negative regulator of hematopoietic stem cell (HSC) proliferation. Loss of Gfi1 induces neutropenia, lymphocyte deficiency, and monocyte accumulation. It is well established that the HSC pool is regulated by osteoblasts; however, whether HSC regulate osteoblasts or MSC differentiation is poorly characterized. We demonstrate that Gfi1 knock-out mice (Gfi1-/-) show a progressive bone loss (osteoporosis), which is in line with the osteoporotic phenotype in patients suffering from chronic idiopathic neutropenia. This project aims to define the underlying mechanism of osteoporosis in Gfi1-/- mice. Moreover, we intend to characterize the influence of a presumably altered HSC pool on osteoblasts within the stem cell niche in Gfi1-/- mice.

转录因子生长因子非依赖性1（GFI 1）是造血干细胞（HSC）增殖的负调节因子。Gfi 1的缺失诱导中性粒细胞减少、淋巴细胞缺乏和单核细胞蓄积。已经确定HSC库受成骨细胞调节;然而，HSC是否调节成骨细胞或MSC分化的特征很差。我们证明，Gfi 1基因敲除小鼠（Gfi 1-/-）表现出进行性骨丢失（骨质疏松症），这与慢性特发性中性粒细胞减少症患者的骨质疏松表型一致。该项目旨在确定Gfi 1-/-小鼠骨质疏松症的潜在机制。此外，我们打算表征一个大概改变的HSC池对成骨细胞内的干细胞龛在Gfi 1-/-小鼠的影响。